Biomolecules, including proteins, peptides and vaccines, make up a large and potent portion of new drugs, and hold great promise for the future of therapeutics. Although oral delivery of these biotherapeutics would be desirable, there is low bioavailability of biomolecules administered by this route due to enzymatic degradation and poor absorption in the GI track, as well as first-pass metabolism of liver. As a result, most biotherapeutics are administered by hypodermic injection, which causes pain or infection, requires to traine personnel and often needs to repeat injections for the patient. Consequently, there exists the need for a minimally invasive, self-administered delivery system for biomolecules.
To address limitations of oral delivery and hypodermic injection, transdemal delivery has been developed to painlessly pierce skin's outer barrier of stratum corneum with the goal to deliver drugs. Transdermal delivery has a variety of advantages compared with the oral delivery. In particular, it is used when there is a significant first-pass effect of the liver that can prematurely metabolize drugs. Transdermal delivery also has advantages over hypodermic injections, which are painful, generate dangerous medical waste and pose the risk of disease transmission by needle re-use. Additionally, the advantage of the transdermal delivery are that it not only crosses the stratum corneum barrier to target dendritic cell in the skin, but dose so using an inexpensive, disposable patch that is simple enough to be suitable for self administration by patients.
The first transdermal system for systemic delivery, a three-day patch that delivers scopolamine to treat motion sickness, was approved for use. A decade later, nicotine patches became the first transdermal blockbuster, raising the profile of transdermal delivery in drugs and for the public in general. Today, there are many transdermal delivery systems for such drugs, such as estraldiol, fentanyl or testosterone, etc. Above descriptions can see in “Prausnitz M. R. et al., Transdermal drug delivery, 2008”; “Lee J. W. et al., Dissolving microneedles for transdermal drug delivery, 2007”; “Kim Y. C. et al., Formulation and coating of microneedles with inactivated influenza virus to improve vaccine stability and immunogenicity, 2009”; and “Sullivan S. P. et al., Minimally invasive protein delivery with rapidly dissolving polymer microneedles, 2008”.
However, in various situations, the delivery speed or flux of a variety of reagents (such as the macromolecular or hydrophilic drugs) is limited by the passive transdermal path, resulting in ineffective treatment. The transdermal delivery method can be allowed the drug to be delivered into the body by passive diffusion, or by external energy including electricity (such as an ion introduction method) or ultrasound (such as an ultrasonic penetration method). Although the drug can be delivered through the stratum corneum and epidermis, the delivery speed of the diffusion through the stratum cuticle is usually a limited step. In addition, in order to achieve an effective dose, a variety of compounds require a delivery speed higher than the speed of simple passive transdermal diffusion.
Furthermore, most conventional transdermal drug delivery patches are quick-release carriers. That is, when external energy is applied, the drug encapsulated in the carrier is released immediately, and the release rate thereof can not be regulated precisely. Therefore, how to control the release rate of the drug encapsulated in the carrier by external energy becomes an important issue.